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Conflicting guidance exists regarding the characterization of nebulization as an aerosol-generating procedure and subsequent risk of transmission of SARS-CoV-2 to healthcare workers.This study sought to address whether SARS-CoV-2 viral load distribution was impacted by bronchodilator delivery via nebulizer versus metered-dose inhaler (MDI).Adults infected with COVID-19 were enrolled and received a single dose of albuterol sulfate nebulized solution (2.5 mg/3 mL via breath-actuated nebulizer with filtered mouthpiece) or albuterol sulfate hydrofluoroalkane inhalation aerosol (90 µg/actuation; two puffs via MDI with spacer) in a randomized crossover sequence. Air and surfaces were sampled at predefined locations within patients’ hospital rooms to assess SARS-CoV-2 dispersion over three periods (baseline, MDI, and nebulizer).Eleven patients received crossover therapy. Six patients had detectable SARS-CoV-2 RNA during one treatment period (n = 3 each for MDI and nebulizer) and one during both treatment periods. No viral RNA was found in the rooms of four (36.4%) patients. Overall, few environmental samples (17/397; 4.3%) contained detectable viral RNA, with no meaningful differences in positivity rate across periods; RNA genome copy numbers were low in positive samples. No correlation between dispersion and patient clinical status or environmental parameters was observed.In this first prospective trial evaluating viral load distribution following use of nebulizer versus MDI in hospitalized patients with COVID-19, low environmental contamination was found regardless of administration method. Findings support the use of either device when needed to treat patients with COVID-19. [ABSTRACT FROM AUTHOR]

Vitamin D3 deficiency has been recognized as a pandemic with serious health consequences including chronic respiratory diseases. Unfortunately, improvement in this situation by using vitamin D supplementation has failed. The direct delivery of 1,25(OH)2-vitamin D3 and its precursor into the respiratory tract, by nebulization, seemed to be a better option, as verified in the presented study. To induce vitamin D deficiency, mice received a diet with 0.05 IU/g cholecalciferol, while control animals were given feed with 0.5 IU/g cholecalciferol. Vitamin-D-deficient mice were exposed to different doses of calcidiol or calcitriol via nebulization for at least 7 days. At the end of the experiment, whole-body plethysmography was conducted. Pulmonary and serum levels of calcitriol were examined using ELISA. The calcitriol concentrations in mice on standard vs. deficient diet were 30.31/18.20 pg/mg (lungs) and 132.24/98.61 pg/mL (serum), respectively. Restoration of the physiological level of calcitriol in vitamin-D-deficient mice required 1-week exposure to 100 pg/g of calcidiol or 5 pg/g of calcitriol. The inhalations did not cause any side changes in murine respiratory function. The presented study revealed the usefulness and safety of chronic inhalation with a bioactive form of vitamin D3 or its precursor for the restoration of physiological calcitriol levels in animals with vitamin D deficiencies.

Acute lung injury in COVID-19 results in diffuse alveolar damage with disruption of the alveolar-capillary barrier, coagulation activation, alveolar fibrin deposition and pulmonary capillary thrombi. Nebulized recombinant tissue plasminogen activator (rt-PA) has the potential to facilitate localized thrombolysis in the alveolar compartment and improve oxygenation. In this proof-of-concept safety study, adults with COVID-19-induced respiratory failure and a 2/FiO2 (P/F) ratio requiring invasive mechanical ventilation (IMV) or non-invasive respiratory support (NIRS) received nebulized rt-PA in two cohorts (C1 and C2), alongside standard of care, between 23 April–30 July 2020 and 21 January–19 February 2021, respectively. Matched historical controls (MHC; n = 18) were used in C1 to explore efficacy. Safety co-primary endpoints were treatment-related bleeds and

Pulmonary bacterial infections present a significant health risk to those with chronic respiratory diseases (CRDs) including cystic fibrosis (CF) and chronic-obstructive pulmonary disease (COPD). With the emergence of antimicrobial resistance (AMR), novel therapeutics are desperately needed to combat the emergence of resistant superbugs. Phage therapy is one possible alternative or adjunct to current antibiotics with activity against antimicrobial-resistant pathogens. How phages are administered will depend on the site of infection. For respiratory infections, a number of factors must be considered to deliver active phages to sites deep within the lung. The inhalation of phages via nebulization is a promising method of delivery to distal lung sites; however, it has been shown to result in a loss of phage viability. Although preliminary studies have assessed the use of nebulization for phage therapy both in vitro and in vivo, the factors that determine phage stability during nebulized delivery have yet to be characterized. This review summarizes current findings on the formulation and stability of liquid phage formulations designed for nebulization, providing insights to maximize phage stability and bactericidal activity via this delivery method.

Background: Awake fiber-optic nasal intubation is a gold standard management of difficult airway in temporal mandibular (TM) joint ankylosis. Aims and Objectives: We compared topical lignocaine nebulization with airway nerve blocks for awake fiber-optic nasal intubation in TM joint ankylosis. Materials and Methods: Fifty patients of either gender were randomly allocated into two groups of 25 each. Group I received 10 ml of 2% lignocaine nebulization over a period for 20 min. Group II received bilateral superior laryngeal nerve block and transtracheal recurrent laryngeal nerve block (each with 2 ml of 2% lignocaine). Awake fiber-optic bronchoscopy-guided nasal intubation was done in all patients. All the patients received sedation during the procedure. The intubation time, intubating conditions, vocal cord position, cough severity, and degree of patient satisfaction were recorded. Student’s t-test was used to analyze parametric data, while the Mann–Whitney U-test was applied to non-parametric data and Fisher’s test to categorical data. P

Disulfiram (DS) has an excellent anti-viral activity; however, its low water-solubility and first-pass metabolism are limiting its clinical applications. Cyclodextrins (CDs) have been used as solubility enhancers and carriers of DS proposed for inhalation to treat SARS-CoV-19. Two types of CDs (hydroxypropyl β-cyclodextrin and sulfobutyl ether β-cyclodextrin) were used to form inclusion complexes with DS, and drug solubility was assessed using spectrophotometric analytical method. Formulations were freeze-dried and characterized using DSC, TGA and FTIR. Nebulization technique was used to assess the potential for generating aerosols. All inclusion complexes are proved to be suitable for inhalation, therefore, potentially effective therapy for further investigation against SARS-CoV-19 is shown.

Objective: To compare the effects of nebulized Ketamine versus nebulized Magnesium Sulfate to prevent post-operative sore throat. Study Design: Quasi-Experimental Study. Place and Duration of Study: Department of Anaesthesia, Combined Military Hospital, Rawalpindi Pakistan, from Sep 2020 to Feb 2021. Methodology: A total of 154 patients who underwent general anaesthesia for elective procedures were randomly included in the study. These patients were divided into two equal Groups, i.e., Group-A (n=77), who received Magnesium Sulphate 250mg in 5ml saline and Group-B (n=77), who received Ketamine 50mg in 5ml saline, respectively. The effects of nebulized Ketamine versus nebulized Magnesium Sulfate to prevent post-operative sore throat, were observed in both the Groups. Results: Both drugs were effective in the prevention of sore throat after extubation. Our study showed that Ketamine nebulization was more effective than Magnesium Sulfate nebulization in preventing sore throat. The frequency of sore throat in Group-A was 54.5% (42 out of 77 patients) as compared to 31.2% (24 out of 77 patients) in Group-B, which was statistically significant (p=0.003). Conclusion: Post-operative sore throat is more effectively controlled with Ketamine as compared to Magnesium Sulfate

The objective of this study was to determine the extent that nebulized glycosylated caffeic acid phenylether ester-4-O-alpha-D-glucopyranoside (G-CAPE) attenuates particulate-induced airway inflammation in healthy horses. Our hypothesis was that nebulization with G-CAPE would result in improved respiratory scores, higher arterial oxygen partial pressure, and less inflammatory airway infiltrates in horses with induced airway inflammation, compared with untreated controls. Five healthy adult horses were housed inside a climate controlled, closed barn on straw bedding and fed ad lib moldy grass hay for 16 days to induce airway inflammation. An experimental crossover study was performed in which animals were treated with 200 mg G-CAPE dissolved in 45 mL of 10% triethanolamine (G-CAPE group) or 45 mL of 10% triethanolamine (CONTROL group), and clinical respiratory scoring, arterial blood gases, and bronchoalveolar lavages (BALs) were collected at predetermined time points up to 24 h post nebulization. While the mean neutrophil percentage decreased in treated horses compared to controls (9.3 ± 2.0 and 16.9 ± 2.4, respectively) at 6 hours post treatment (t = 6 h), the difference did not achieve statistical significance (p = 0.1154). Blood gas analysis did not differ significantly between groups. There was a significant difference in the mean respiratory scores of G-CAPE-treated horses between baseline and at 1-h post treatment (from 3.2 ± 0.7 to 1.6 ± 0.7, p = 0.0013). This study demonstrates that a single nebulized dose of G-CAPE decreased clinical respiratory scores 1 h post administration and decreased BAL percentage of neutrophils 6 h post administration in horses with particulate induced airway inflammation. This compound shows promise as an anti-inflammatory and warrants further investigation.

Objective: To compare the outcome of Salbutamol nebulization with normal saline (placebo) in transient tachypnea of the newborn. Study Design: Comparative prospective study. Place and Duration of Study: Department of Neonatal Medicine, Military Hospital Rawalpindi, from Jan 2017 to Mar 2018. Methodology: Sixty term neonates with respiratory rate >60 breaths/min and transient tachypnea of newborn score of ≥4 were enrolled. They were randomly allocated to two equal groups. Group-1 received Salbutamol nebulization (0.15 mg/kg) while Group-2 received normal Saline (placebo) nebulization. Results: The mean gestational age was 38.31±1.28 weeks, while the average birth weight was 2.97±0.27 kg. The mean change in transient tachypnea of newborn score with Salbutamol nebulization was 5.63±1.22, while 0.63±1.54 with normal Saline nebulization. Likewise, the mean change in respiratory rate with Salbutamol was 9.80±2.05, while -3.73±2.57 with normal saline. Conclusion: This study demonstrated nebulized Salbutamol as an effective tool in reversing transient tachypnea of newborns with decreasing respiratory rate compared to normal saline nebulization (placebo).

Central nervous system (CNS) disorders, such as psychiatric disorders, neurodegeneration, chronic pain, stroke, brain tumor, spinal cord injury, and many other CNS diseases, would hugely benefit from specific and potent peptide pharmaceuticals and their low inherent toxicity. The delivery of peptides to the brain is challenging due to their low metabolic stability, which decreases their duration of action, poor penetration of the blood-brain barrier (BBB), and their incompatibility with oral administration, typically resulting in the need for parenteral administration. These challenges limit peptides' clinical application and explain the interest in alternative routes of peptide administration, particularly nose-to-brain (N-to-B) delivery, which allows protein and peptide drugs to reach the brain noninvasively. N-to-B delivery can be a convenient method for rapidly targeting the CNS, bypassing the BBB, and minimizing systemic exposure; the olfactory and trigeminal nerves provide a unique pathway to the brain and the external environment. This review highlights the intranasal delivery of drugs, focusing on peptide delivery, illustrating various clinical applications, nasal delivery devices, and the scope and limitations of this approach. [ABSTRACT FROM AUTHOR]

Disulfiram (DS), known as an anti-alcoholism drug, has shown a potent antiviral activity. Still, the potential clinical application of DS is limited by its low water solubility and rapid metabolism. Cyclodextrins (CDs) have been widely used to improve the solubility of drugs in water. In this study, five concentrations of hydroxypropyl β-cyclodextrin (HP) and sulfobutyl ether β-cyclodextrin (SBE) were used to form inclusion complexes of DS for enhanced solubility. Solutions were freeze-dried, and the interaction between DS and CD was characterized using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), and Fourier transform infrared spectroscopy (FTIR). In addition, the nebulization properties of the DS–CD solutions were studied. The aqueous solubility of DS increased significantly when loaded to either of both CDs. The phase solubility of both complexes was a linear function of the CD concentration (AL type). Furthermore, physicochemical characterization studies showed a potent inclusion of the drug in the CD–DS complexes. Aerosolization studies demonstrated that these formulations are suitable for inhalation. Overall, the CD inclusion complexes have great potential for the enhancement of DS solubility. However, further studies are needed to assess the efficacy of DS–CD inclusion complexes against SARS-CoV-2 via nebulization. [ABSTRACT FROM AUTHOR]

Background: Scientists have been facing numerous challenges in the development of an effective therapeutic strategy for the treatment of COVID-19 pneumonia. Several studies have suggested that improving patient immunity and reducing lung injury induced by SARS-CoV-2 may be effective for treating patients with COVID-19. Methods: A pilot trial of nebulization therapy with exosomes of mesenchymal stem cells (MSCs) was performed on seven patients with COVID-19 pneumonia. Exosomes secreted from MSCs were collected and purified using multiple ultrafiltration steps. All patients were treated with nebulization of MSC-derived exosomes, and primary safety and efficacy outcomes were evaluated. Results: Our clinical study demonstrated that nebulization of MSC-derived exosomes is a novel method that might be utilized in the treatment of COVID-19 pneumonia. Nebulization of MSC-derived exosomes did not induce acute allergic or secondary allergic reactions but did promote the absorption of pulmonary lesions and reduce the duration of hospitalization for mild cases of COVID-19 pneumonia. Conclusions: Nebulization of MSC-derived exosomes is a safe, effective, and simple method, and their application at the beginning of treatment may be more beneficial. Trial Registration: Chinese Clinical Trial Registry, ChiCTR2000030261. Registered on 26 February 2020. [ABSTRACT FROM AUTHOR]

Developing new effective treatment strategies to overcome the rise in multi-drug resistant tuberculosis cases (MDR-TB) represents a global challenge. A host-directed therapy (HDT), acting on the host immune response rather than Mtb directly, could address these resistance issues. We developed an HDT for targeted TB treatment, using All Trans Retinoic Acid (ATRA)-loaded nanoparticles (NPs) that are suitable for nebulization. Efficacy studies conducted on THP-1 differentiated cells infected with the H37Ra avirulent Mycobacterium tuberculosis (Mtb) strain, have shown a dose-dependent reduction in H37Ra growth as determined by the BACT/ALERT® system. Confocal microscopy images showed efficient and extensive cellular delivery of ATRA-PLGA NPs into THP-1-derived macrophages. A commercially available vibrating mesh nebulizer was used to generate nanoparticle-loaded droplets with a mass median aerodynamic diameter of 2.13 μm as measured by cascade impaction, and a volumetric median diameter of 4.09 μm as measured by laser diffraction. In an adult breathing simulation experiment, 65.1% of the ATRA PLGA-NP dose was inhaled. This targeted inhaled HDT could offer a new adjunctive TB treatment option that could enhance current dosage regimens leading to better patient prognosis and a decreasing incidence of MDR-TB. [ABSTRACT FROM AUTHOR]

The SARS‐CoV‐2 pandemic, which suddenly appeared at the beginning of 2020, revealed our knowledge deficits in terms of ventilation and air pollution control. It took many weeks to realize that aerosols are the main route of transmission. The initial attempt to hold back these aerosols through textile masks seemed almost helpless, although there is sufficient knowledge about the retention capacity of fabric filters for aerosols. In the absence of a sufficient number of permanently installed heating, ventilation, and air conditioning systems, three main approaches are pursued: (a) increasing the air exchange rate by supplying fresh air, (b) using mobile air purifiers, and (c) disinfection by introducing active substances into the room air. This article discusses the feasibility of these different approaches critically. It also provides experimental results of air exchange measurements in a school classroom that is equipped with a built‐in fan for supplying fresh air. With such a fan and a window tilted at the appropriate distance, an air exchange rate of 5/h can be set at a low power level and without any significant noise pollution. Heat balance calculations show that no additional heat exchanger is necessary in a normal classroom with outside temperatures above 10°C. Furthermore, a commercial mobile air purifier is studied in a chamber and a test room setup in order to examine and evaluate the efficiency of such devices against viable viruses under controlled and realistic conditions. For this purpose, bacteriophages of the type MS2 are used. Both window ventilation and air purifiers were found to be suitable to reduce the concentration of phages in the room. [ABSTRACT FROM AUTHOR]

Background: Awake fiberoptic intubation (AFOI) is the gold standard for managing a difficult airway. To make the patient comfortable and cooperative during the procedure, many drugs such as benzodiazepines, opioids, or dexmedetomidine are used. Most of these intravenously given drugs may cause respiratory depression and hypoxia. Aim: We compared the efficacy of dexmedetomidine through nebulization and transtracheal route with intravenous routes with the primary aim of comparing patient tolerance score (PTS) and secondary objectives of comparing sedation score, cough score, and total duration required for awake fiberoptic nasotracheal intubation. Settings and Design: This study was a prospective randomized double-blind study. Subjects and Methods: Seventy-six patients, scheduled for elective surgery requiring AFOI between 18 and 75 years, were included in the study. They were randomly divided into two groups of 38 each. Group I patients received intravenous dexmedetomidine 1 μg.kg−1 and Group L patients received local dexmedetomidine through nebulization 0.5 μg.kg−1 and transtracheal injection 0.5 μg.kg−1. Statistical Analysis Used: Statistical Package for the Social Sciences version 22 was used. Results: Patients who received dexmedetomidine through nebulization and transtracheal route have significantly better PTSs and less cough scores as compared to patients who received dexmedetomidine by intravenous route (P < 0.05). Hemodynamic parameters and sedation scores between the two groups were statistically insignificant (P > 0.05). The time required for the procedure was significantly less in Group L compared to Group I (P < 0.05). Conclusion: Dexmedetomidine by nebulization and transtracheal route provides optimal conditions for AFOI with good patient tolerance and less cough score as compared to the intravenous route. [ABSTRACT FROM AUTHOR]

Background: Cystic fibrosis (CF) patients are prone to recurrent multi-drug-resistant (MDR) bacterial lung infections. Under this scenario, phage therapy has been proposed as a promising tool. However, the limited number of reported cases hampers the understanding of clinical outcomes. Anti-phage immune responses have often been overlooked and only described following invasive routes of administration., Methods: Three monophage treatments against Staphylococcus aureus and/or Pseudomonas aeruginosa lung infections were conducted in cystic fibrosis patients. In-house phage preparations were nebulized over 10 days with standard-of-care antibiotics. Clinical indicators, bacterial counts, phage and antibiotic susceptibility, phage detection, and immune responses were monitored., Findings: Bacterial load was reduced by 3-6 log in two of the treatments. No adverse events were described. Phages remained in sputum up to 33 days after completion of the treatment. In all cases, phage-neutralizing antibodies were detected in serum from 10 to 42 days post treatment, with this being the first report of anti-phage antibodies after nebulized therapy., Conclusions: Nebulized phage therapy reduced bacterial load, improving quality of life even without bacterial eradication. The emergence of antibodies emphasizes the importance of long-term monitoring to better understand clinical outcomes. These findings encourage the use of personalized monophage therapies in contrast to ready-to-use cocktails, which might induce undesirable antibody generation., Funding: This study was supported by the Spanish Ministry of Science, Innovation and Universities; Generalitat Valenciana; and a crowdfunding in collaboration with the Spanish Cystic Fibrosis Foundation., Competing Interests: Declaration of interests P.D.-C. is cofounder of Evolving Therapeutics SL and a member of its scientific advisory board, and P.E.T. is cofounder of Felix Biotechnology, Inc., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The delivery of mRNA into the lungs is the key to solving infectious and intractable diseases that frequently occur in the lungs. Since inhalation using a nebulizer is the most promising method for mRNA delivery into the lungs, there have been many attempts toward adapting lipid nanoparticles for mRNA inhalation. However, conventional lipid nanoparticles, which have shown great effectiveness for systemic delivery of mRNA and intramuscular vaccination, are not effective for pulmonary delivery due to their structural instability during nebulization and their inability to adapt to the pulmonary microenvironment. To address these issues, we developed an ionizable liposome-mRNA lipocomplex (iLPX). iLPX has a highly ordered lipid bilayer structure, which increases stability during nebulization, and its poly(ethylene glycol)-free composition allows it to infiltrate the low serum environment and the pulmonary surfactant layer in the lungs. We selected an inhalation-optimized iLPX (IH-iLPX) using a multistep screening procedure that mimics the pulmonary delivery process of inhaled nanoparticles. The IH-iLPX showed a higher transfection efficiency in the lungs compared to conventional lipid nanoparticles after inhalation with no observed toxicity in vivo . Furthermore, analysis of lung distribution revealed even protein expression in the deep lungs, with effective delivery to epithelial cells. This study provides insights into the challenges and solutions related to the development of inhaled mRNA pulmonary therapeutics.

Background: Aerosol therapy is commonly used during treatment with high-flow nasal cannula (HFNC) in the intensive care unit (ICU). Heated humidification inside the HFNC tubing circuit leads to unwanted condensation, which may greatly limit the efficiency of drug delivery. In this study, we aimed to investigate whether a novel humidification system, which decouples temperature and humidity control, can improve the delivered dose., Methods: In a bench study setup, fluorescein sodium solution was nebulized using a vibrating-mesh nebulizer in an infant HFNC circuit to measure the delivered dose, with a conventional versus a novel decoupled humidifier. The deposition of fluorescein inside each breathing circuit component and a final collection filter at the end of the nasal cannula was collected and quantified with a UV-vis spectrometer. Droplet sizes at different sections of the breathing circuit were measured by laser diffraction. Three air flow rates: 5, 10 and 15 L/min, and two nebulizer positions: (1) at the humidifier and (2) after the inspiratory tube, were tested., Results: The delivered dose decreased with increasing flow rate for the conventional setup and was higher when the nebulizer was placed after the inspiratory tube. Turning off the conventional humidifier 10 minutes before and during nebulization did not improve the delivered dose. The decoupled humidifier achieved a significantly higher (p = .002) delivered dose than the conventional setup. The highest delivered dose obtained by the decoupled humidifier was 62.4% when the nebulizer was placed after the humidifier, while the highest dose obtained for the conventional humidifier was 36.3% by placing the nebulizer after the inspiratory tube., Conclusions: In this bench study, we found that the delivered dose for an infant HFNC nebulization setup could be improved significantly by decoupling temperature and humidity control inside the HFNC circuit, as it reduced drug deposition inside the breathing circuit., (Copyright © 2024 by Daedalus Enterprises.)

Introduction Care of the airway is an essential part of the management of patients receiving mechanical ventilation. If the airway is not properly managed, an endotracheal airway can result in retained secretions, airway obstructions, and infections. These complications may prolong mechanical ventilation duration and length of hospital stay and may increase the cost of affordability. Hypertonic saline nebulized suctioning is a technique used to lessen the duration of mechanical air flow and enhance airway clearance, which helps patients on mechanical ventilation breathe easier. Aim The objective of the study is to assess the effectiveness of nebulization with hypertonic saline on arterial blood gas parameters among mechanically ventilated patients. Methods The quasi-experimental design adopted with thirty-five mechanically ventilated samples was chosen using a non-probability purposive sample technique. Following the pre-test in the endotracheal tube, nebulization was given with 2 ml of hypertonic saline over 15-20 mins, two times each day, to the mechanically ventilated patients. Post-test was carried out about 15-20 minutes after the procedure using arterial blood gas analysis results were obtained and interpreted. Results The study reveals that the p values corresponding to the arterial blood gas parameters PCo2, pO2, and HCo3 are less than 0.01 and are significant at a 1% level, and arterial blood gas (ABG) pH is less than 0.05 and is significant at a 5% level; hence there is a high significant difference between the pre-test and post-test mean scores of arterial blood gas parameters PCo2, pO2, HCo3, and ABG pH. Hence, the study concluded that nebulization with hypertonic saline for patients with mechanical ventilators is more effective in improving arterial blood gas parameters., Competing Interests: Human subjects: Consent was obtained or waived by all participants in this study. Institutional Ethical Committee of Sri Ramaswamy Memorial Medical College Hospital and Research Centre issued approval 2990/IEC/2021. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work., (Copyright © 2024, M et al.)

Background: During invasive mechanical ventilation, where medical gases are very dry and the upper airway is bypassed, appropriate gas conditioning and humidification are mandatory at all times. Results of in vitro studies suggest that dry gases may improve lung deposition during nebulization, but this has not been confirmed through in vivo studies. The objective of this study was to measure gas humidity under multiple conditions to better describe gas hygrometry when heated humidifiers are turned off., Methods: We measured, on a bench, the hygrometry of different gases at steady state: medical gases, at the Y-piece without humidifier, with the humidifier switched off, and with humidifier switched on. We measured gas humidity every 10-60 s during dynamic conditions after switching off the heated humidifier and after switching on the heated humidifier. Hygrometry was measured by using the psychrometric method with at least 3 measurements for each tested condition., Results: We performed 287 psychrometric measurements in different situations. The mean ± SD gas absolute humidity at steady state during different conditions were the following: 1.6 ± 0.2 mg H 2 O/L for the medical gases, 4.5 ± 0.9 mg H 2 O/L at the Y-piece without humidifier, 9.1 ± 0.3 mg H 2 O/L at the Y-piece with heated humidifier turned off, and 34.2 ± 2.2 mg H 2 O/L at the Y-piece with the heated humidifier turned on. During the dynamic evaluation, after turning off the humidifier, humidity was < 30 mg H 2 O/L after a few minutes, attained 15 mg H 2 O/L after 15 min, and was below 10 mg H 2 O/L after 1 h but never reached the level of dry medical gases. After turning on the heated humidifier, the gas hygrometry reached 30 mg H 2 O/L after 5 min., Conclusions: When heated humidifiers are turned off, gas humidity levels are very low but not as low as medical gases. The clinical impact of repeated shutdowns is unknown. As recommended, heated humidifiers should never be turned off during nebulization., (Copyright © 2024 by Daedalus Enterprises.)

Chronic obstructive pulmonary disease (COPD) is a prevalent lung disease usually resulting from cigarette smoking (CS). Cigarette smoking induces oxidative stress, which causes inflammation and alveolar epithelial cell apoptosis and represents a compelling therapeutic target for COPD. Purified human platelet-derived exosome product (PEP) is endowed with antioxidant enzymes and immunomodulatory molecules that mediate tissue repair. In this study, a murine model of CS-induced emphysema was used to determine whether nebulized PEP can influence the development of CS-induced emphysema through the mitigation of oxidative stress and inflammation in the lung. Nebulization of PEP effectively delivered the PEP vesicles into the alveolar region, with evidence of their uptake by type I and type II alveolar epithelial cells and macrophages. Lung function testing and morphometric assessment showed a significant attenuation of CS-induced emphysema in mice treated with nebulized PEP thrice weekly for 4 weeks. Whole lung immuno-oncology RNA sequencing analysis revealed that PEP suppressed several CS-induced cell injuries and inflammatory pathways. Validation of inflammatory cytokines and apoptotic protein expression on the lung tissue revealed that mice treated with PEP had significantly lower levels of S100A8/A9 expressing macrophages, higher levels of CD4+/FOXP3+ Treg cells, and reduced NF-κB activation, inflammatory cytokine production, and apoptotic proteins expression. Further validation using in vitro cell culture showed that pretreatment of alveolar epithelial cells with PEP significantly attenuated CS extract-induced apoptotic cell death. These data show that nebulization of exosomes like PEP can effectively deliver exosome cargo into the lung, mitigate CS-induced emphysema in mice, and suppress oxidative lung injury, inflammation, and apoptotic alveolar epithelial cell death., Competing Interests: Declaration of competing interest A.B., T.P., M.S., and P.S., along with Mayo Clinic, have ownership rights to RION Inc.; C.P. is a scientist employed by Rion Inc. RV has received consulting fees ($10,000) from Rion, Inc and is named as an inventor on a pending international patent #: PCT/US2024/014217)., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Bronchiolitis is the most common lower respiratory tract infection in children. The management guidelines recommend only supportive measures; however, there is an increasing burden for bronchiolitis especially in developing countries. The use of nebulized hypertonic saline may aid in decreasing hospital stay and decrease the global burden of the disease.Objective: To compare between the efficacy of hypertonic saline versus normal saline in reducing duration of hospital admission and improving symptoms of acute bronchiolitis.Patients and methods: A randomized comparative clinical trial included 90 children with acute bronchiolitis, conducted at Al-Azhar University Hospital (New Damietta) during the period from October 2019 till June 2020. Patients were randomly assigned into 2 groups; 45 patients received 3% hypertonic saline nebulization (group 1), and 45 patients received 0.9% normal saline nebulization (group 2). Efficacy of treatment was assessed through duration of hospitalization and oxygen supplementation, and severity of respiratory distress.Results: there was no significant difference between both groups as regard to age, sex, baseline clinical severity score and O2 saturation. After treatment, patients who received nebulized hypertonic saline showed less duration of hospitalization (62.3±20.8 hours vs 76.8± 26.1 hours; p=0.001), less duration of O2 therapy (16.2±6.0 hours vs 25.3±5.4 hours; p=0.01). As regard to severity clinical score, patients received nebulized hypertonic saline showed significant improvement started within 24 hours from admission (P=

Nowadays, due to a higher resistance to drugs, antibiotics, and antiviral medicaments, new ways of fighting pathogens are intensively studied. The alternatives for synthesized compositions are natural products, most of which have been known in natural medicine for a long time. One of the best-known and intensively investigated groups are essential oils (EOs) and their compositions. However, it is worth noting that the method of application can play a second crucial part in the effectiveness of the antimicrobial activity. EOs possess various natural compounds which exhibit antimicrobial activity. One of the compositions which is based on the five main ingredients of eucalyptus, cinnamon, clove, rosemary, and lemon is named “five thieves’ oil” (Polish name: olejek pięciu złodziei) (5TO) and is used in natural medicine. In this study, we focused on the droplet size distribution of 5TO during the nebulization process, evaluated by the microscopic droplet size analysis (MDSA) method. Furthermore, viscosity studies, as well as UV-Vis of the 5TO suspensions in medical solvents such as physiological salt and hyaluronic acid, were presented, along with measurements of refractive index, turbidity, pH, contact angle, and surface tension. Additional studies on the biological activity of 5TO solutions were made on the P. aeruginosa strain NFT3. This study opens a way for the possible use of 5TO solutions or emulsion systems for active antimicrobial applications, i.e., for surface spraying.

Aminoglycosides are a family of rapidly bactericidal antibiotics that often remain active against resistant Gram-negative bacterial infections. Over the past decade, their use in critically ill patients has been refined; however, due to their renal and cochleovestibular toxicity, their indications in the treatment of sepsis and septic shock have been gradually reduced. This article reviews the spectrum of activity, mode of action, and methods for optimizing the efficacy of aminoglycosides. We discuss the current indications for aminoglycosides, with an emphasis on multidrug-resistant Gram-negative bacteria, such as extended-spectrum β-lactamase-producing Enterobacterales, carbapenemase-producing Enterobacterales, multidrug-resistant Pseudomonas aeruginosa, and carbapenem-resistant Acinetobacter baumannii. Additionally, we review the evidence for the use of nebulized aminoglycosides.

Patients with COVID-19 may complicate their evolution with thromboembolic events. Incidence of thromboembolic complications are high and also, patients with the critically-ill disease showed evidence of microthrombi and microangiopathy in the lung probably due to endothelial damage by directly and indirectly injured endothelial and epithelial cells. Pulmonary embolism, deep venous thrombosis and arterial embolism were reported in patients with COVID-19, and several analytical abnormal coagulation parameters have been described as well. D-dimer, longer coagulation times and lower platelet counts have been associated with poor outcomes. The use of anticoagulation or high doses of prophylactic heparin is controversial. Despite the use of anticoagulation or high prophylactic dose of heparin have been associated with better outcomes in observational studies, only in patients with non-critically ill disease benefits for anticoagulation was observed. In critically-ill patient, anticoagulation was not associated with better outcomes. Other measures such as antiplatelet therapy, fibrinolytic therapy or nebulized anticoagulants are being studied in ongoing clinical trials. [ABSTRACT FROM AUTHOR]

Purpose: To evaluate ocular surface status and corneal higher‐order aberrations after a new ocular nebulization therapy combined with meibomian gland massage for the treatment of meibomian gland dysfunction (MGD). Patients and methods: This prospective randomized study involved 38 patients diagnosed with MGD. Subjects were classified into two groups: the nebulization and meibomian gland massage group (or NB group, 14 patients, 28 eyes) and the eye drop group (or ED group, 24 patients, 48 eyes). Azithromycin solution and esculin and digitalis glycoside eye drops were tested in the therapy. Best‐corrected visual acuity (BCVA) testing; noncontact tonometry; fundoscopy; the Ocular Surface Disease Index (OSDI) questionnaire; tear film assessment encompassing tear meniscus height (TMH) and non‐invasive keratograph breakup time (NIKBUT); corneal fluorescein staining; the Schirmer I test (SIT); and anterior, posterior and total corneal aberrations were evaluated at 1 and 3 months after treatment. Results: At 3 months, the NB group showed significantly better improvement than the ED group in terms of TMH (0.23 ± 0.04 versus 0.19 ± 0.05, p = 0.002) and first breakup time (f‐BUT; 7.42 ± 2.49 versus 5.53 ± 2.12, p = 0.001). The average breakup time (Av‐BUT) of the NB group was significantly longer than that of the ED group at 1 month (9.52 ± 2.70 versus 8.02 ± 2.33, p = 0.013) and 3 months (5.53 ± 2.12 versus 8.35 ± 2.38, p = 0.018). Both groups achieved improvement in corneal fluorescein staining (CFS) and SIT results at 1 and 3 months (p < 0.05). At the 3‐month follow‐up, anterior corneal trefoil aberrations decreased significantly in the NB group (p = 0.008), and improvements in anterior corneal coma aberrations and posterior corneal higher‐order aberrations (HOAs) were observed in the ED group (p < 0.05) over the 4 mm pupil zone. Over a 6 mm zone at 3 months, anterior, posterior and total trefoil aberrations as well as total HOAs were significantly decreased in the NB group (p < 0.05), while posterior HOAs and trefoil aberrations were found to be decreased in the ED group (p < 0.05). For individual Zernike terms, anterior and total corneal Z(3, −3) showed decreases over the 4 and 6 mm zones, while no improvement was detected in the NB group at 3 months. Conclusion: In terms of comfort and visual quality, nebulization therapy combined with meibomian gland massage to deliver azithromycin solution and esculin and digitalis glycoside eye drops appears to be more effective in treating clinical symptoms and signs of MGD than simply applying esculin and digitalis glycoside eye drops. [ABSTRACT FROM AUTHOR]

Background: Bronchiolitis is a common cause of illness and hospitalization in infants and young children. The effectiveness of various bronchodilators remains unclear. This study was conducted to assess the efficacy of nebulized magnesium sulfate in hospitalized children with moderate bronchiolitis in the age group of 1-24 months. Subjects and Methods: This was a prospective observational study done from December 2018 to June 2020. All children with moderate bronchiolitis (clinical severity score [CSS]-4-8) meeting inclusion/exclusion criteria were enrolled. A detailed history, demographic profile, CSS and oxygen saturation in room air, and heart rate were recorded. They were given two doses of magnesium sulfate in the form of nebulization for 10 min each, at 30 min apart. The children were assessed for CSS at 0 h, 1 h, and 4 h after nebulization. The children were considered improved if CSS <4 at the end of 4 h. The children were monitored for adverse reactions of magnesium sulfate. Results: Sixty children were enrolled. The mean age was 7.5 ± 6.47 months. Most children (51.7%) were in 1-6 months. The mean CSS scores at 0 h, 1 h, and 4 h were 6 ± 1.008, 2.95 ± 1.395, and 2.40 ± 1.564, respectively (P = < 0.001). Fifty-three (88.3%) children improved and seven (11.7%) children did not improve. In nonimproved group, subanalysis was done and found hypoxia (odds ratio - 12.6) as a significant risk factor. Flushing was the most common adverse effect noticed in eight (13.3%) children. Conclusions: Children with moderate bronchiolitis were improved with nebulized magnesium sulfate. [ABSTRACT FROM AUTHOR]

Background: Allaying anxiety and providing calm children in the operating room is a challenging task for anesthesiologists. This study was designed to compare the use of nebulized dexmedetomidine and ketamine for premedication in pediatric patients under general anesthesia. Methods: Seventy patients, aged 2 to 8 years of both sexes, with American Society of Anesthesiologists physical status I/II scheduled for hernia repair surgery under general anesthesia, were randomized to two equal groups using a computer-generated random number table. Patients in group D received dexmedetomidine (2 μg/kg), and patients in group K received ketamine (2 mg/kg) by a jet nebulizer before the induction of anesthesia. The study’s primary objective was comparing the level of sedation, which was achieved at 30 min after a study drug administration using the Ramsay sedation scale, between the two groups. The secondary objectives were the two-group comparison of parental separation anxiety scale, acceptance of the mask, hemodynamic variables, recovery time, incidence of emergence agitation, and adverse events. Results: The median Ramsay sedation scale at 30 min was 3 (1–4) in group D and 3 (1–3) in group K (P = 0.002). Patients in group D had a more acceptable parental separation anxiety scale (P = 0.001) and a satisfactory mask acceptance scale (P = 0.042). Conclusions: Nebulized dexmedetomidine (2 μg/kg) provided better sedation along with smooth parental separation and satisfactory mask acceptance during induction of anesthesia with a similar emergence agitation profile and adverse reactions compared to nebulized ketamine in pediatric patients. [ABSTRACT FROM AUTHOR]

We analyze changes in circulating platelets in COVID-19 positive patients who received conventional treatment Dexamethasone and Enoxaparin (Dexa-Enoxa) compared to patients treated with conventional therapy plus nebulization with alkaline hypertonic ibuprofenate (AHI). Results show that after 24 h of nebulization with AHI, circulating platelets shows an increase about 40% at 24 h and reach 65% at 96 h. In patients with platelets content below 200,000 by microliter the increase was 49% and 79% at 24 and 96 h respectively. In patients with platelets above 200,000 by microliter the increase was 24% and 31% at 24 and 96 h, respectively. The increase of platelets via AHI was similar in both, men and women. To evaluate whether this action of AHI was related to platelets from COVID-19 positive patients or also for healthy people, two controls were included: one of them with 10 healthy volunteers and another one with COVID-19 positive patients hospitalized and treated only with Dexa-Enoxa. Results show that, in healthy volunteers, the number of circulating platelets remains unchanged even after 7 days of treatment with AHI. In COVID-19 positive patients treated only with Dexa-Enoxa for 4 days, platelets increased only 16%. [ABSTRACT FROM AUTHOR]

Background: Endotracheal intubation is the prominent cause of airway mucosal injury which results in postoperative sore throat (POST), with an incidence of 21%-65% if left unresolved, it produces significant agony and annoyance to the patient. Objective: The aim of the present study was to compare the hemodynamic effect of nebulized dexamethasone and nebulized ketamine on postoperative sore throat after thyroid surgeries. Patients and methods: This prospective controlled randomized double-blind study was carried out in Zagazig University Hospitals during the period from January to July 2021, included 72 patients of both gender in the age group 21-50 years, undergoing thyroidectomy under general anesthesia. Results: There was statistically significant increase of the severity and incidence of sore throat in the control groups immediately postoperatively, 2, 6, 12 and 24 hours postoperatively among the studied groups. While, there was significant difference between dexamethasone groups and ketamine group regarding the severity and incidence of sore throat immediatley, 2, and 6 hours (hr) postoperatively. Conclusions: We concluded that nebulized dexamethsone may be considered as a safe alternative to nebulized ketamine for decreasing POST. [ABSTRACT FROM AUTHOR]

The favipiravir proliposomal is a powder formulation for pulmonary delivery by nebulization, prepared and characterized by film deposition on carrier method. The formulations have good flow properties and upon hydration, liposome vesicles were seen within 2-3 minutes. According to the results of SEM studies the surface morphology was coarse and non-porous. The DSC and XRD studies confirm that the favipiravir drug is crystalline, whereas the FPL6 is amorphous. In-vitro nebulization studies performed using a twin stage impinger (TSI) revealed that the nebulization time ranges from 12.95 to 14.3 minutes. The aerosol mass output and rate ranges from 44.31 to 54.28 %, and 0.17 to 0.22 mg/min. respectively. The respirable fraction ranges from 8.14 to 12.31%. The FPL6 formulation has a higher respirable fraction of 12.31%, which is available for therapeutic action in the lungs and stable. The results showed that the favipiravir proliposomal formulation was suitable for pulmonary drug delivery via nebulization. [ABSTRACT FROM AUTHOR]

BACKGROUND: Aerosol delivery via high-flow nasal cannula (HFNC) has attracted clinical interest in recent years. However, both HFNC and nebulization are categorized as aerosol-generating procedures (AGPs). In vitro studies raised concerns that AGPs had high transmission risk. Very few in vivo studies examined fugitive aerosols with nebulization via HFNC, and effective methods to mitigate aerosol dispersion are unknown. METHODS: Two HFNC devices (Airvo 2 and Vapotherm) with or without a vibrating mesh nebulizer were compared; HFNC alone, surgical mask over HFNC interface, and HFNC with face tent scavenger were used in a random order for 9 healthy volunteers. Fugitive aerosol concentrations at sizes of 0.3-10.0 lm were continuously measured by particle sizers placed at 1 and 3 ft from participants. On a different day, 6 of the 9 participants received 6 additional nebulizer treatments via vibrating mesh nebulizer or small-volume nebulizer (SVN) with a face mask or a mouthpiece with/without an expiratory filter. In vitro simulation was employed to quantify inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 and Vapotherm. RESULTS: Compared to baseline, neither HFNC device generated higher aerosol concentrations. Compared to HFNC alone, vibrating mesh nebulizer via Airvo 2 generated higher 0.3-1.0 lm particles (all P < .05), but vibrating mesh nebulizer via Vapotherm did not. Concentrations of 1.0-3.0 lm particles with vibrating mesh nebulizer via Airvo 2 were similar with vibrating mesh nebulizer and a mouthpiece/face mask but less than SVN with a mouthpiece/face mask (all P < .05). Placing a surgical mask over HFNC during nebulization reduced 0.5-1.0 lm particles (all P < .05) to levels similar to the use of a nebulizer with mouthpiece and expiratory filter. In vitro the inhaled dose of albuterol with vibrating mesh nebulizer via Airvo 2 was 6 6 times higher than vibrating mesh nebulizer via Vapotherm. CONCLUSIONS: During aerosol delivery via HFNC, Airvo 2 generated higher inhaled dose and consequently higher fugitive aerosols than Vapotherm. Simple measures, such as placing a surgical mask over nasal cannula during nebulization via HFNC, could effectively reduce fugitive aerosol concentrations. [ABSTRACT FROM AUTHOR]

BACKGROUND: Ribavirin is an antiviral drug that for many years has been administered to the lungs by aerosolization. Despite advancements in oral delivery routes, there has been a renewed interested in delivering ribavirin via the pulmonary system in select patients and the severely ill. The vibrating mesh nebulizer was previously demonstrated to be an effective alternative to the small-particle aerosol generator in particle size, chemical makeup, and concentrations of the ribavirin before and after nebulization. However, the antiviral activity of ribavirin has never been examined. We sought to study ribavirin's activity before and after nebulization via vibrating mesh nebulizer. METHODS: We grew and infected human epithelial type 2 cells and primary airway epithelial cells with respiratory syncytial virus (RSV). We then compared the antiviral effect of non-nebulized (control) and aerosolized ribavirin to untreated controls. We used traditional plaque assay and real-time polymerase chain reaction to determine the quantity of virus. RESULTS: Both non-nebulized (control) and nebulized ribavirin reduced the size of RSV plaques compared to untreated controls. Additionally, the non-nebulized and nebulized ribavirin equally inhibited RSV replication. There were no statistically significant differences between the non-nebulized and nebulized ribavirin across all time points. CONCLUSIONS: The vibrating mesh nebulizer did not affect the antiviral properties of nebulized ribavirin when compared to non-nebulized drug. Our findings add supporting evidence for the use of the vibrating mesh nebulizer in the administration of inhaled ribavirin. [ABSTRACT FROM AUTHOR]

BACKGROUND: Fugitive aerosol concentrations generated by different nebulizers and interfaces in vivo and mitigation of aerosol dispersion into the environment with various commercially available devices are not known. METHODS: Nine healthy volunteers were given 3 mL saline with a small-volume nebulizer (SVN) or vibrating mesh nebulizer (VMN) with a mouthpiece, a mouthpiece with an exhalation filter, an aerosol mask with open ports for SVN and a valved face mask for VMN, and a face mask with a scavenger (Exhalo) in random order. Five of the participants received treatments using a face tent scavenger (Vapotherm) and a mask with exhalation filter with SVN and VMN in a random order. Treatments were performed in an ICU room with 2 particle counters positioned 1 and 3 ft from participants measuring aerosol concentrations at sizes of 0.3-10.0 lm at baseline, before, during, and after each treatment. RESULTS: Fugitive aerosol concentrations were higher with SVN than VMN and higher with a face mask than a mouthpiece. Adding an exhalation filter to a mouthpiece reduced aerosol concentrations of 0.3-1.0 lm in size for VMN and 0.3-3.0 lm for SVN (all P < .05). An Exhalo scavenger over the mask reduced 0.5-3.0 lm sized particle concentrations for SVN (all P < .05) but not VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosol concentrations regardless of the nebulizer type. CONCLUSIONS: SVN produced higher fugitive aerosol concentrations than VMN, whereas face masks generated higher aerosol concentrations than mouthpieces. Adding an exhalation filter to the mouthpiece or a scavenger to the face mask reduced aerosol concentrations for both SVN and VMN. Vapotherm scavenger and filter face mask reduced fugitive aerosols as effectively as a mouthpiece with an exhalation filter. This study provides guidance for reducing fugitive aerosol emissions from nebulizers in clinical practice. [ABSTRACT FROM AUTHOR]

After shifting away from invasive mechanical ventilation and intratracheal instillation of surfactant toward non-invasive ventilation with nasal CPAP and less invasive surfactant administration in order to prevent bronchopulmonary dysplasia in preterm infants with respiratory distress syndrome, fully non-invasive surfactant nebulization is the next Holy Grail in neonatology. Here we review the characteristics of animal-derived (clinical) and new advanced synthetic lung surfactants and improvements in nebulization technology required to secure optimal lung deposition and effectivity of non-invasive lung surfactant administration. Studies in surfactant-deficient animals and preterm infants have demonstrated the safety and potential of non-invasive surfactant administration, but also provide new directions for the development of synthetic lung surfactant destined for aerosol delivery, implementation of breath-actuated nebulization and optimization of nasal CPAP, nebulizer circuit and nasal interface. Surfactant nebulization may offer a truly non-invasive option for surfactant delivery to preterm infants in the near future.

Abstract The coronavirus disease 2019 (COVID‐19) pandemic has become a serious burden on global public health. Although therapeutic drugs against COVID‐19 have been used in many countries, their efficacy is still limited. We here reported nanobody (Nb) phage display libraries derived from four camels immunized with the SARS‐CoV‐2 spike receptor‐binding domain (RBD), from which 381 Nbs were identified to recognize SARS‐CoV‐2‐RBD. Furthermore, seven Nbs were shown to block interaction of human angiotensin‐converting enzyme 2 (ACE2) with SARS‐CoV‐2‐RBD variants and two Nbs blocked the interaction of human ACE2 with bat‐SL‐CoV‐WIV1‐RBD and SARS‐CoV‐1‐RBD. Among these candidates, Nb11‐59 exhibited the highest activity against authentic SARS‐CoV‐2 with 50% neutralizing dose (ND50) of 0.55 μg/ml. Nb11‐59 can be produced on large scale in Pichia pastoris, with 20 g/L titer and 99.36% purity. It also showed good stability profile, and nebulization did not impact its stability. Overall, Nb11‐59 might be a promising prophylactic and therapeutic molecule against COVID‐19, especially through inhalation delivery.

Abstract Background and Aims Postoperative sore throat (POST) is common after endotracheal intubation making patients uncomfortable and anxious in postoperative period. The present study was undertaken to compare efficacy of equal dose of dexamethasone in preventing POST via three different routes, i.e., intravenous, topical, and nebulization before surgery. Methods and Results The present prospective double-blind randomized parallel group trial included 190 patients of either sex above 18 years, American Society of Anesthesiologists (ASA) physical status I–II posted for laparoscopic cholecystectomy. The patients were divided into three groups. Patients in group N were nebulized with 8 mg dexamethasone prior to surgery, patients in group I received intravenous dexamethasone (8 mg) before induction of anesthesia, while patients in group C were intubated with endotracheal tube which was pretreated (cuff soaked in dexamethasone 8 mg). The severity of POST and hoarseness of voice was determined by interviewing patients after 24-h of completion of surgery. Incidence of POST decreased in all patients with maximum decrease in group N (18%), while 30.8% in group I and 30.4% in group C. This decrease was not statistically significant when compared to group I (p 0.14) as well as group C (p 0.15). Incidence of hoarseness significantly decreased in group N (15.6%) as compared to group I (40.3%) as well as group C (39.1%). This decrease was statistically significant when compared to group I (p 0.005) as well as group C (p 0.009). Conclusions Topical dexamethasone (group C) is as effective as intravenous dexamethasone in decreasing incidence of POST, while both the techniques are not effective in decreasing hoarseness of voice. Nebulization is most effective method in decreasing POST as well as hoarseness. Trial Registration CTRI/2017/08/009524 dated 29 August 2017 prospectively.

Inhalation therapy is the cornerstone of chronic obstructive pulmonary disease (COPD) management. However, for many COPD patients who are managed at home, nebulization therapy offers an effective alternative treatment and fulfills the gap of catering to the specific population of patients who are unable to use handheld inhaler devices appropriately. The present review highlights key aspects, namely selection of the right beneficiaries for home nebulization, available drugs in nebulized formulations for the treatment of COPD, and the importance of care, cleaning, and maintenance, which are prerequisites for ensuring successful nebulization therapy.

Administration of sub-dissociative doses of ketamine is used via intranasal (IN) and intravenous routes in the pediatric emergency department for managing acute pain. Due to difficulties in both obtaining intravenous access and compliance with IN medications in children, administration of ketamine via breath-actuated nebulizer can serve as a valuable modality for timely analgesia in children where dosing titration is patient controlled. We describe five pediatric patients who received ketamine via breath-actuated nebulizer at 0.75 mg/kg, 1 mg/kg, and 1.5 mg/kg, with all patients experiencing a decrease in pain score. This case series introduces ketamine inhalation as a modality for managing pain in children.

Intro duction: Awake fiberoptic bronchoscope-guided intubation is the preferred airway management strategy in a patient with a difficult airway and limited mouth opening. The aim is to compare the efficacy of nebulization and airway nerve block using lignocaine to provide airway anesthesia in awake patients using fiberoptic bronchoscope for nasal intubation to make the patient comfortable, cooperative, and agreeable. Methods: In this randomized, prospective, single-blinded study, sixty adult patients scheduled for oral cancer surgeries were divided into two equal groups. Nebulization with 4% lignocaine (10 ml) was performed in Group N, and superior bilateral laryngeal and trans-laryngeal recurrent laryngeal nerve blocks used 2% lignocaine (2 ml) were given in Group B. Nasotracheal intubation using fiberoptic bronchoscope were performed. Intravenous midazolam and fentanyl were used for sedation and analgesia. We recorded the ease of intubation, coughing episodes, vocal cord status, hemodynamic variables, patient recall, and lignocaine toxicity. Student's t-test and Chi-square tests were used for appropriate data. Statistical significance was considered for P < 0.05 (SPSS Version 20, IBM, USA). Results: The intubation time was shorter with better intubating conditions in Group B (120.3 ± 42.6 s) than Group N (200.4 ± 60.3 s) (P < 0.001). Cough severity and patient recall for untoward effects were lower in Group B. Intubation were done successfully in all patients. Conclusion: Airway nerve blocks provided better airway anesthesia characterized by easier fiberoptic intubation and patient comfort than lignocaine nebulization. Nebulization can be considered a suitable alternative when nerve blocks are not feasible due to distorted neck anatomy.

Nebulization of lipid-phage nanocomplex for the management of respiratory infections associated with intracellular Staphylococcus aureus. [Display omitted] • EPC liposome-phage K nanocomplex showed excellent aerodynamic performance and protection of phage against the nebulization-induced stresses. • SPC-phage K and EPC-phage K had promoted the killing efficiency against S. aureus whereas HSPC-phage K showed impaired infectivity. • EPC-phage K exhibited the best intracellular bacterial killing with no relapse of infection. • EPC-phage K managed the infection in 3D epithelial cell spheroid more efficiently than free phage and SPC-phage K and HSPC-phage K. Host cell invasion with strong antibiotics evading is a major feature of respiratory Staphylococcus aureus infections with severe recurrence. Bacteriophage (phage) therapy and design of liposomal phage to target intracellular pathogens have been described recently. The practicality for pulmonary delivery of liposomal phage, and how formulation compositions affecting the aerosolization and intracellular bacterial killing remain unexplored. In the present study, three commonly used phospholipids (SPC, EPC, and HSPC) were selected to investigate their ability for phage K nebulization and intracellular therapy in the form of liposome-phage nanocomplexes. The three lipid nanocarriers showed protection on phage K upon mesh nebulization and the pulmonary deposition efficiency was influenced by the lipid used. Moreover, the intracellular bacterial killing was strongly depended on the lipid types, where EPC-phage exhibited the best killing performance with no relapsing. Phage K with the aid of EPC liposomes was also observed to manage the tissue infection in a 3D spheroid model more effectively than other groups. Altogether, this novel EPC liposome-phage nanocomplex can be a promising formulation approach that enables inhalable phage to manage respiratory infections caused by bacteria strongly associated with human epithelial cells. [ABSTRACT FROM AUTHOR]

Verteporfin (VER), a photosensitizer used in macular degeneration therapy, has shown promise in controlling macrophage polarization and alleviating inflammation in acute lung injury (ALI)/acute respiratory distress syndrome (ARDS). However, its hydrophobicity, limited bioavailability, and side effects hinder its therapeutic potential. In this study, we aimed to enhance the therapeutic potential of VER through pulmonary nebulized drug delivery for ALI/ARDS treatment. We combined hydrophilic hyaluronic acid (HA) with an oil-in-water system containing a poly(lactic acid- co -glycolic acid) (PLGA) copolymer of VER to synthesize HA@PLGA-VER (PHV) nanoparticles with favorable surface characteristics to improve the bioavailability and targeting ability of VER. PHV possesses suitable electrical properties, a narrow size distribution (approximately 200 nm), and favorable stability. In vitro and in vivo studies demonstrated the excellent biocompatibility, safety, and anti-inflammatory responses of the PHV by suppressing M1 macrophage polarization while inducing M2 polarization. The in vivo experiments indicated that the treatment with aerosolized nano-VER (PHV) allowed more drugs to accumulate and penetrate into the lungs, improved the pulmonary function and attenuated lung injury, and mortality of ALI mice, achieving improved therapeutic outcomes. These findings highlight the potential of PHV as a promising delivery system via nebulization for enhancing the therapeutic effects of VER in ALI/ARDS. [ABSTRACT FROM AUTHOR]

Ultrasonic atomization is a widely used technology. As the atomization device, lead zirconate titanate (PZT) and lithium niobate (LN) are comparatively investigated through experimental and numerical schemes. However, knowledge on a profitable scheme by which to efficiently deliver the atomized particles into the tracheal tube remains unclear. In this study, the physical difference of the transmission efficiency of water particles atomized by PZT and LN devices was measured. The water particles atomized by PZT and LN were injected into a human airway model including a nasal cavity and bronchial tube. The distribution of the amount of transmitted particles deposited at each of the monitoring positions was then estimated using the results of image analysis of color intensity. As a result, the atomized particles of the PZT device, which produced larger particles than the LN device, were more strongly affected by inertia and tended to be deposited at the area closer to the entrance of the nasal cavity. In contrast, the particles produced by the LN device tended to be transmitted deeper into the trachea. The experimental results indicated that the particle size distribution of PZT and LN, which have quite different maximum sizes of particles, largely influences the spatial distribution characteristics of particle deposition along the airway from the nasal cavity to the trachea. [Display omitted] • Knowledge on a profitable scheme by which to efficiently deliver atomized particles into the tracheal tube remains unclear. • This paper investigated physical difference of transmission efficiency of water particles atomized by PZT and LN. • Particle size distribution largely influences spatial distribution of particle deposition along the airway from the nasal cavity to the trachea. [ABSTRACT FROM AUTHOR]

Lung cancer is one of the most common causes of high mortality worldwide. Current treatment strategies, e.g., surgery, radiotherapy, chemotherapy, and immunotherapy, insufficiently affect the overall outcome. In this study, we used curcumin as a natural photosensitizer in photodynamic therapy and encapsulated it in liposomes consisting of stabilizing tetraether lipids aiming for a pulmonary drug delivery system against lung cancer. The liposomes with either hydrolyzed glycerol-dialkyl-glycerol tetraether (hGDGT) in different ratios or hydrolyzed glycerol-dialkyl-nonitol tetraether (hGDNT) were prepared by dual centrifugation (DC), an innovative method for liposome preparation. The liposomes' physicochemical characteristics before and after nebulization and other nebulization characteristics confirmed their suitability. Morphological characterization using atomic force and transmission electron microscopy showed proper vesicular structures indicative of liposomes. Qualitative and quantitative uptake of the curcumin-loaded liposomes in lung adenocarcinoma (A549) cells was visualized and proven. Phototoxic effects of the liposomes were detected on A549 cells, showing decreased cell viability. The generation of reactive oxygen species required for PDT and disruption of mitochondrial membrane potential were confirmed. Moreover, the chorioallantoic membrane (CAM) model was used to further evaluate biocompatibility and photodynamic efficacy in a 3D cell culture context. Photodynamic efficacy was assessed by PET/CT after nebulization of the liposomes onto the xenografted tumors on the CAM with subsequent irradiation. The physicochemical properties and the efficacy of tetraether lipid liposomes encapsulating curcumin, especially liposomes containing hGDNT, in 2D and 3D cell cultures seem promising for future PDT usage against lung cancer. [Display omitted] [ABSTRACT FROM AUTHOR]

In clinical practice, several emergencies may threaten the life of patients, and these emergencies can be unpredictable and challenging. During the coronavirus disease 2019 pandemic, in January 2023, a patient developed respiratory distress caused by coronavirus, but was unable to access respiratory support due to shortages of medical resources, intensive care unit beds and ventilators. The medical staff quickly created a portable high-flow atomized oxygen therapy apparatus consisting of a simple breathing bag connected to a nebulizer to provide breathing support. In addition, the Ambulatory Surgery Center, The First Affiliated Hospital of Anhui Medical University (Hefei, China) witnessed a case of severe laryngeal spasm after tracheal extubation during the recovery period from general anesthesia. Due to the lack of an anesthesia machine nebulizer, the aforementioned device was used to provide oxygen under pressure and initiate treatment to quickly relieve the symptoms of laryngeal obstruction. The present case report describes how the medical staff quickly applied emergency airway management skills and knowledge to create a portable high-flow atomized oxygen therapy apparatus in a resource-poor setting to save the lives of two patients. [ABSTRACT FROM AUTHOR]

In recent years, ivermectin (IVM), an antiparasitic drug of low water solubility and poor oral bioavailability, has shown a profound effect on inflammatory mediators involved in diseases, such as acute lung injury, lung fibrosis, and COVID-19. In order to maximize drug bioavailability, polymeric nanoparticles can be delivered through nebulizers for pulmonary administration. The aim of this study was to prepare IVM-loaded polycaprolactone (PCL) nanoparticles (NPs) by solvent evaporation method. Box-Benkhen design (BBD) was used to optimize entrapment efficiency (Y 1), percent drug release after 6 h (Y 2), particle size (Y 3), and zeta potential (Y 4). A study was conducted examining the effects of three independent variables: PCL-IVM ratio (A), polyvinyl alcohol (PVA) concentration (B), and sonication time (C). The optimized formula was also compared to the oral IVM dispersion for lung deposition, in-vivo behavior, and pharmacokinetic parameters. The optimized IVM-PCL-NPs formulation was spherical in shape with entrapment efficiency (% EE) of 93.99 ± 0.96 %, about 62.71 ± 0.53 % released after 6 h, particle size of 100.07 ± 0.73 nm and zeta potential of -3.30 ± 0.23 mV. Comparing the optimized formulation to IVM-dispersion, the optimized formulation demonstrated greater bioavailability with greater area under the curve AUC 0–t of 710.91 ± 15.22 μg.ml−1.h for lung and 637.97 ± 15.43 μg.ml−1.h for plasma. Based on the results, the optimized NPs accumulated better in lung tissues, exhibiting a twofold longer residence time (MRT 4.78 ± 0.55 h) than the IVM-dispersion (MRT 2.64 ± 0.64 h). The optimized nanoparticle formulation also achieved higher c max (194.90 ± 5.01 μg/ml), and lower k el (0.21 ± 0.04 h −1) in lungs. Additionally, the level of inflammatory mediators was markedly reduced. To conclude, inhalable IVM-PCL-NPs formulation was suitable for the pulmonary delivery and may be one of the most promising approaches to increase IVM bioavailability for the successful treatment of a variety of lung diseases. [Display omitted] [ABSTRACT FROM AUTHOR]

The efficiency of lung drug delivery of nebulized drugs is governed by aerosol quality, which depends both on the aerosolization process itself but also on the properties of aerosol precursors. This paper determines physicochemical properties of four analogous micro-suspensions of a micronized steroid (budesonide, BUD) and seeks relationships between these properties and the quality of the aerosol emitted from a vibrating mesh nebulizer (VMN). Despite the same BUD content in all tested pharmaceutical products, their physicochemical characteristics (liquid surface tension, viscosity, electric conductivity, BUD crystal size, suspension stability, etc.) are not identical. The differences have a weak influence on droplet size distribution in the mists emitted from the VMN and on theoretical (calculated) regional aerosol deposition in the respiratory system but, simultaneously, there is an influence on the amount of BUD converted by the nebulizer to aerosol available for inhalation. It is demonstrated that the maximum inhaled BUD dose is below 80–90% of the label dose, depending on the nebulized formulation. It shows that nebulization of BUD suspensions in VMN is sensitive to minor dissimilarities among analogous (generic) pharmaceutics. The potential clinical relevance of these findings is discussed.

Bacteriophages have been identified as a potential treatment option to treat lung infection in the context of antibiotic resistance. We performed a preclinical study to predict the efficacy of delivery of bacteriophages against Pseudomonas aeruginosa (PA) when administered via nebulization during mechanical ventilation (MV). We selected a mix of four anti-PA phages containing two Podoviridae and two Myoviridae, with a coverage of 87.8% (36/41) on an international PA reference panel. When administered via nebulization, a loss of 0.30–0.65 log of infective phage titers was measured. No difference between jet, ultrasonic and mesh nebulizers was observed in terms of loss of phage viability, but a higher output was measured with the mesh nebulizer. Interestingly, Myoviridae are significantly more sensitive to nebulization than Podoviridae since their long tail is much more prone to damage. Phage nebulization has been measured as compatible with humidified ventilation. Based on in vitro measurement, the lung deposition prediction of viable phage particles ranges from 6% to 26% of the phages loaded in the nebulizer. Further, 8% to 15% of lung deposition was measured by scintigraphy in three macaques. A phage dose of 1 × 109 PFU/mL nebulized by the mesh nebulizer during MV predicts an efficient dose in the lung against PA, comparable with the dose chosen to define the susceptibility of the strain.

(1) Background: Colistin-only susceptible (COS) Acinetobacter baumannii (AB) ventilator-associated pneumonia (VAP) represents a clinical challenge in the Intensive Care Unit (ICU) due to the negligible lung diffusion of this molecule and the low-grade evidence on efficacy of its nebulization. (2) Methods: We conducted a prospective observational study on 134 ICU patients with COS-AB VAP to describe the ‘real life’ clinical use of high-dose (5 MIU q8) aerosolized colistin, using a vibrating mesh nebulizer. Lung pharmacokinetics and microbiome features were investigated. (3) Results: Patients were enrolled during the COVID-19 pandemic with the ICU presenting a SAPS II of 42 [32–57]. At VAP diagnosis, the median PaO2/FiO2 was 120 [100–164], 40.3% were in septic shock, and 24.6% had secondary bacteremia. The twenty-eight day mortality was 50.7% with 60.4% and 40.3% rates of clinical cure and microbiological eradication, respectively. We did not observe any drug-related adverse events. Epithelial lining fluid colistin concentrations were far above the CRAB minimal-inhibitory concentration and the duration of nebulized therapy was an independent predictor of microbiological eradication (12 [9.75–14] vs. 7 [4–13] days, OR (95% CI): 1.069 (1.003–1.138), p = 0.039). (4) Conclusions: High-dose and prolonged colistin nebulization, using a vibrating mesh, was a safe adjunctive therapeutic strategy for COS-AB VAP. Its right place and efficacy in this setting warrant investigation in interventional studies.

The Northwestern pond turtle (Actinemys marmorata) is native to Washington State, USA and has developed a grossly evident form of shell disease affecting a large percentage of the free-ranging population in this state. Emydomyces testavorans is a novel fungus in the order Onygenales that is the presumed causative agent for shell disease in the Northwestern pond turtle. Terbinafine hydrochloride is a lipophilic allylamine broad-spectrum antifungal that penetrates keratin and concentrates in the stratum corneum. This study evaluated the drug concentration in the plasma and keratin of 18 Northwestern pond turtles after nebulization with 18 mg terbinafine solution (2 mg/ml) once a day for 28 days. Blood and keratin samples were collected serially during the course of treatment, and for 14 days following the last dose. Plasma and keratin were analyzed by high-performance liquid chromatography. No significant concentrations of terbinafine were found in the plasma of the turtles. Terbinafine in turtle keratin peaked after 16 days of treatment and maintained therapeutic concentrations for 14 days posttreatment. Turtle shell lesions also showed signs of clinical improvement posttherapy. Nebulization of terbinafine is recommended for the treatment of shell disease secondary to Emydomyces testavorans; however, pulse antifungal therapy is likely needed to prevent disease from reoccurring. [ABSTRACT FROM AUTHOR]